The hardline group has seized tracts of territory in Syria and neighboring Iraq, where it has also been targeted by US-led forces since last July.
Ten of the civilians killed were children and six were women, the Observatory said. It said 90 members of the al-Qaeda-affiliated Nusra Front were also killed in the air strikes, which started on September 23.
The United States has said it takes reports of civilian casualties seriously and says it has a process to investigate each allegation.
Washington justified its action in Syria under Article 51 of the UN Charter, which covers an individual or collective right to self-defense against armed attack.
Around 220,000 people have been killed in Syria’s conflict, which is now in its fourth year, the United Nations has said.
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